Genetic targeting of protease activated receptor 2 reduces inflammatory astrogliosis and improves recovery of function after spinal cord injury

Neurobiology of Disease
Maja RadulovicIsobel A Scarisbrick

Abstract

Inflammatory-astrogliosis exacerbates damage in the injured spinal cord and limits repair. Here we identify Protease Activated Receptor 2 (PAR2) as an essential regulator of these events with mice lacking the PAR2 gene showing greater improvements in motor coordination and strength after compression-spinal cord injury (SCI) compared to wild type littermates. Molecular profiling of the injury epicenter, and spinal segments above and below, demonstrated that mice lacking PAR2 had significantly attenuated elevations in key hallmarks of astrogliosis (glial fibrillary acidic protein (GFAP), vimentin and neurocan) and in expression of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor (TNF) and interleukin-1 beta (IL-1β)). SCI in PAR2-/- mice was also accompanied by improved preservation of protein kinase C gamma (PKCγ)-immunopositive corticospinal axons and reductions in GFAP-immunoreactivity, expression of the pro-apoptotic marker BCL2-interacting mediator of cell death (BIM), and in signal transducer and activator of transcription 3 (STAT3). The potential mechanistic link between PAR2, STAT3 and astrogliosis was further investigated in primary astrocytes to reveal that the SCI-related serine protease, neurosin...Continue Reading

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Citations

Mar 31, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Shannon M JonesA Phillip Owens
Aug 18, 2016·Biological Chemistry·Hyesook Yoon, Isobel A Scarisbrick
Jun 21, 2018·Scientific Reports·Chan-Il ChoiIsobel A Scarisbrick
Apr 25, 2020·Molecular Neurobiology·Hadi Abou-El-HassanIbrahim Omeis
Mar 11, 2020·The Journal of Clinical Investigation·Allison C BilliNicole L Ward
Jan 28, 2021·International Journal of Molecular Sciences·Petra MrozkovaJiri Palecek
Feb 20, 2021·ASN Neuro·Michael Brenner, Albee Messing

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